Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Factor XI Deficiency”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8Linked to original sources
PubMed1999

Age estimates of two common mutations causing factor XI deficiency: recent genetic drift is not necessary for elevated disease incidence among Ashkenazi Jews.

The type II and type III mutations at the FXI locus, which cause coagulation factor XI deficiency, have high frequencies in Jewish populations. The type III mutation is largely restricted to Ashkenazi Jews, but the type II mutation is observed at high frequency in both Ashkenazi and Iraqi Jews, suggesting the possibility that the mutation appeared before the separation of these communities. Here we report estimates of the ages of the type II and type III mutations, based on the observed distribution of allelic variants at a flanking microsatellite marker (D4S171). The results are consistent with a recent origin for the type III mutation but suggest that the type II mutation appeared >120 generations ago. This finding demonstrates that the high frequency of the type II mutation among Jews is independent of the demographic upheavals among Ashkenazi Jews in the 16th and 17th centuries.

Alleles↗
PubMed2000

A novel mutation that leads to a congenital factor XI deficiency in a Japanese family.

We have identified a novel mutation leading to a congenital deficiency of the coagulation factor XI (FXI) in a Japanese family. A propositus was a 42-year-old female patient without bleeding tendency. Coagulant activity and the antigen level of FXI in her plasma were below the detectable range. The nucleotide sequences of the FXI gene of this patient were determined by a direct sequence method established in this study. A novel nonsense mutation (CAA; Gly263 --> TAA; stop) was identified in exon 8 of the FXI gene. Her parents are first cousins, and a polymerase chain reaction-restriction-fragment length polymorphism analysis revealed that her parents were heterozygous at this nucleotide position. This patient inherited mutant alleles from her parents and is homozygous at this nucleotide position. The nonsense mutation in the FXI gene is responsible for her deficiency of FXI.

Adult↗
PubMed2001

Severe factor XI deficiency caused by compound heterozygosity for the type III mutation and a novel insertion in exon 9 (codons 324/325 +G).

We investigated a 42-year-old Caucasian woman with severe factor XI deficiency and her family members. Restriction enzyme analysis and DNA sequencing revealed compound heterozygosity in the patient for the known type III mutation, which is a Phe283Leu amino acid substitution in the fourth apple domain causing impaired dimerization and secretion, and for a novel frameshift mutation in exon 9 (codons 324/325 +G), leading to premature termination with lack of parts of the fourth apple domain and the downstream serine protease domain.

Adult↗
PubMed2005

Factor XI deficiency database: an interactive web database of mutations, phenotypes, and structural analysis tools.

Factor XI (FXI) is the zymogen of a serine protease enzyme in the intrinsic pathway of blood coagulation and is an important factor in the creation of a stable fibrin clot. Deficiency of FXI leads to an injury-related bleeding disorder and is remarkable for the lack of correlation between bleeding symptoms and FXI coagulant activity (FXI:C). The FXI protein is composed of five domains: four tandem repeat domains of approximately 80 residues known as Apple (Ap) domains, and the catalytic serine protease (Sp) domain. A total of 65 mutations throughout the FXI gene (F11) have been reported in FXI deficient patients. An interactive web database of these mutations has been created (www.FactorXI.org) that integrates the phenotypic data with genetic data and structural homology models for the five FXI domains. The database provides a central repository for all reported genetic alterations within F11. With the use of recently developed visualization tools, each mutation can be highlighted on the structural models of the FXI domains together with an appropriate survey of patient data, such as FXI:C levels and FXI antigen levels. The database also enables new F11 mutations to be interpreted. The interactive design of this database will lead to a more comprehensive comparative understanding of the genetic factors that influence bleeding risk.

DNA Mutational Analysis↗
PubMed1998

Anaesthetic management of a parturient with severe congenital factor XI deficiency undergoing caesarean section for triplet pregnancy.

The report describes the anaesthetic management of a Jewish patient of Ashkenazi descent with severe factor XI deficiency complicated by thrombocytopenia for caesarean section for triplets at the 35th week of gestation. Perioperative management consisted of sustained replacement therapy with fresh frozen plasma and platelets until the sixth postoperative day. General anaesthesia was used for the procedure. No other maternal or neonatal complications occurred.

Journal Article↗
PubMed1987

Identification of factor XI deficiency in Holstein-Friesian cattle in Britain.

Blood coagulation tests were performed on dairy cattle in a herd with haemorrhagic problems on a farm in Gloucestershire. The characteristic pattern of prolonged partial thromboplastin time with normal prothrombin time and thrombin time was shown to be associated with a partial factor XI deficiency, a congenital defect previously identified in cattle in North America.

Animals↗
PubMed2004

Is the assessment of von Willebrand disease prevalence an achievable challenge? The example of the French Basque Country where blood group O and factor XI deficiency are highly prevalent.

The diagnosis of type I von Willebrand disease (VWD) is not straightforward because of the absence of a single clear-cut biological criteria and the interference of several acquired conditions on phenotype expression. We illustrate here this challenge with the French Basque population characterised by a marked high frequency in both blood group O and factor XI deficiency. From this example one may question the validity of epidemiological studies reporting on VWD prevalence.

ABO Blood-Group System↗
PubMed2003

Eighteen unrelated patients with factor XI deficiency, four novel mutations and a 100% detection rate by denaturing high-performance liquid chromatography.

Factor XI (FXI) deficiency is an autosomal bleeding disorder of variable severity. Inheritance is not completely recessive as heterozygotes may display a distinct, if mild, bleeding tendency. Eighteen unrelated FXI-deficient patients were screened blind by fluorescent single-stranded conformation polymorphism (F-SSCP) analysis and denaturing high-performance liquid chromatography (dHPLC). Mutations were detected in 14 of the 18 patients ( approximately 78%) by F-SSCP and in all 18 patients by dHPLC. Dideoxy sequencing confirmed the mutations in all 18 patients: eight of the mutations being novel (four of which were in previously reported patients). This showed dHPLC to be a highly sensitive, reliable technique for mutation screening in heterogeneous disorders.

Chromatography, High Pressure Liquid↗
PubMed2003

Inherited factor XI deficiency confers no protection against acute myocardial infarction.

BACKGROUND AND PURPOSE: Factor XI (FXI) contributes to thrombin generation thereby affecting fibrin formation and to down regulation of fibrinolysis by activation of thrombin-activatable fibrinolysis inhibitor (TAFI). The purpose of this study was to evaluate whether patients with severe FXI deficiency are protected against acute myocardial infarction (AMI). METHODS: The incidence of AMI in patients with severe FXI deficiency (FXI activity less than 15 U dL(-1)) whose age was 35 years or more was compared to the incidence of AMI in age and gender matched persons of the general population. Atherosclerotic risk factors were assessed in FXI deficient patients and blood was tested for prothrombotic parameters such as FV Leiden, prothrombin G20210A, lupus anticoagulant, and platelet membrane polymorphisms. The common mutations causing FXI deficiency in Jews were also examined. RESULTS: Of 96 patients with severe FXI deficiency (55 women and 41 men) 16 had a history of AMI (6 women and 10 men). The median age at the time of AMI was 64.5 for women and 58 for men. The calculated annual rate of AMI in men was similar to the expected in the general Israeli population, whereas in women it was almost 2-fold higher, but this difference did not reach statistical significance. One or more atherosclerotic risk factors were observed in 13 of 16 patients (81.3%) with AMI compared to 44 of 79 patients (55.7%) without AMI (P < 0.001). The frequency distributions of platelet polymorphisms and of prothrombotic polymorphisms were not different between patients with severe FXI deficiency who experienced or not an AMI. None of the patients had lupus anticoagulant. The common genotypes which cause FXI deficiency in Jews were similarly distributed in patients with and without AMI. CONCLUSIONS: Severe FXI deficiency does not confer protection against AMI.

Adult↗
PubMed2000

Molecular genetic analysis of factor XI deficiency: identification of five novel gene alterations and the origin of type II mutation in Portuguese families.

Coagulation factor XI (FXI) deficiency is an inherited autosomal recessive mild bleeding disorder. In this study, we report the molecular genetic analysis of FXI deficiency in six unrelated families of Portuguese origin. The Jewish type II mutation was found in two families, of seemingly Portuguese origin. Haplotype analysis in these families demonstrated that this mutation is of Jewish origin. In the remaining families, five novel FXI mutations have been identified. Two of these mutations (FXI IVS K -10T-->A and FXI 1026G-->T, cd 324) affect the FXI pre-mRNA splicing. A further two (FXI 307 ins AAGCAAT, cd 85 and FXI 1072 del A, cd 340) introduce frameshifts leading to premature termination codons. The FXI splicing mutation, 1026G-->T cd 324, was found in compound heterozygosity with missense mutation FXI K518N. Analysis of the FXI mRNA from the latter genotype demonstrated new donor splice site usage. All reported mutations most likely result in functional null-alleles. In addition, three novel polymorphisms have been identified: at nt -138 in intron A, at codon D125 in exon 5 and at codon T249 in exon 8.

Alleles↗